IN VIVO EVALUATION OF THE CHRONIC TOXIC EFFECTS OF REPEATED ADMINISTRATION OF THE C-4 COMPOSITION AT DIFFERENT DOSES IN RABBITS

Background: Repeated-dose toxicity studies are required to identify cumulative adverse effects, target-organ injury, dose-response patterns, and the reversibility of treatment-related changes before a pharmacologically active composition advances in development. Objective: This study evaluated the safety of the C-4 composition after once-daily oral administration to rabbits at 4, 8, or 16 mg/kg for 90 consecutive days. Methods: Rabbits were assigned to a distilled-water control group or one of three dose groups. Clinical condition, behavior, body weight, peripheral blood indices, serum biochemical markers, relative organ weights, gross pathology, and hematoxylineosin histology of major organs were assessed. Quantitative figures in the source study report mean ± SEM for four animals per group. Results: No statistically significant reatment-related differences were reported for hemoglobin, erythrocytes, leukocytes, platelets, selected erythrocyte indices, serum total protein, glucose, urea, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, or body-weight gain (p > 0.05). Relative organ-weight coefficients were broadly comparable across groups. Most examined tissues retained normal architecture, with mild lymphoid activation and vascular congestion described as non-destructive findings. At 16 mg/kg, however, uneven myocardial congestion and microfoci of myolysis with little or no cellular reaction were reported. Conclusion: The available dataset shows no overt systemic, hematological, or serum-biochemical toxicity at 4-16 mg/kg over 90 days. The 4- and 8 mg/kg doses appear well tolerated. A definitive no-observed-adverse effect level should not be assigned until the high-dose cardiac finding, sample-size discrepancy, and unreported recovery, coagulation, and renal-excretory outcomes are clarified.

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